Molecular Biochemistry Flashcards
(39 cards)
What 3 compounds are needed to begin de novo pyrimidine synthesis?
- Glutamine
- CO2
- ATP
How do the purine and pyrimidine de novo synthesis pathways differ in terms of their starting materials?
Purine = Start with a sugar (PRPP) and add a base Pyrimidine = Start with a base (orotic acid) and add a sugar (PRPP)
What is the rate limiting step of de novo pyrimidine synthesis?
Carbamoyl phosphate synthetase II converting Glutamine, CO2 and ATP to carbamoyl phosphate
What is carbamoyl phosphate converted to for pyrimidine synthesis? What is required for this conversion?
Orotic acid, needs aspartate
What is the defective enzyme in orotic acid uria? What is its normal function?
UMP synthase defeciency
Normally (orotic acid + PRPP) is converted to UMP by UMP synthase
What are the key features of orotic aciduria?
- Orotic acid in urine without hyperammoniemia (indicating that it is not a urea cycle problem)
- Failure to thrive
- Megaloblastic anemia
How do you treat orotic aciduria?
Increase uridine in the diet
Once UMP is made what are the final steps in the pyrimidine synthesis pathway?
UMP –> UTP –>CTP
and
UMP–>UTP–>dUTP–>dUMP–>dTMP via deoxyribonucleotide reductase and thymidylate synthase
What enzyme does hydroxyurea inhibit?
Deoxyribonucleotide reductase, no UTP–>dUTP
What enzyme does 5FU inhibit?
Thymidylate synthase, no dUMP –>dTMP
What cofactor does thymidylate synthase require?
Tetrahydrofolate which is converted to dihydrofolate in the process of making dTMP
What are the starting blocks for making a purine?
PRPP + Glycine + Aspartate + Glutamine
What is the rate limiting step in de novo purine synthesis?
Glutamine PRPP Amidotransferase
What are the substrates for, cofactors of, and products of Glutamine PRPP Amidotransferase?
Substrates: PRPP (from Ribose-5-P) + glycine +glutamine +CO2
Cofactor: THF
Products: IMP
What is IMP converted to in the purine synthesis pathway? What enzyme is involved?
IMP –> GMP via IMP Dehydrogenase
and
IMP –> AMP
What is the first part of the purine salvage pathway?
GTP, IMP, and ATP are converted to guanosine, inosine and adenosine respectively
In the purine salvage pathway, what is adenosine converted into? By what enzyme?
Inosine, adenosine deaminase
What does adenosine deaminase deficiency lead to?
SCID, decreased T and B cells with no thymic shadow and the triad:
- Severe recurrent infections
- Chronic diarrhea
- Failure to thrive
What is guanosine converted to in the purine salvage pathway?
Guanine
What is hypoxanthine converted into in the purine salvage pathway?
Hypoxanthine
What are guanine and hypoxanthine both converted to in the purine salvage pathway? What enzyme is involved?
Xanthine, enzyme = xanthine oxidase
What is xanthine converted to in the purine salvage pathway? What enzyme is involved?
Uric acid, xanthine oxidase
What is the role of HGPRT in the purine salvage pathway?
Enzyme that takes Guanine back to GMP and Hypoxanthine back to IMP
What deficiency leads to Lesch-Nyhan syndrome and how does it present?
HGPRT Deficiency
- No pruine salvage = Increased uric acid production
- Gout + MR +Aggressive behavior +Involuntary movements
